Dimethylformamide → 4-{Cycloheptylidene[4-(5-hydroxy-1-pentyn-1-yl)phenyl]methyl}phenol

HRID 1716150Notes

Reaction equation

HRID 1716150 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:16]2[CH2:23][CH2:22]CC[CH2:19][CH2:18][CH2:17]2)[C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[CH:24](N(CC)C(C)C)(C)C.[CH2:33](O)[CH2:34][CH2:35][C:36]#C.[NH4+].[Cl-].CN([CH:44]=[O:45])C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.O>[C:16]1(=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:33]#[C:34][CH2:35][CH2:36][CH2:44][OH:45])=[CH:3][CH:4]=2)[C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)[CH2:23][CH2:22][CH2:24][CH2:19][CH2:18][CH2:17]1

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 793464-Pentyn-1-olHCID 81531DiisopropylethylamineHCID 686544754-[(4-Bromophenyl)(cyclooctylidene)methyl]phenol

Product 1

HCID 111992024-{Cycloheptylidene[4-(5-hydroxy-1-pentyn-1-yl)phenyl]methyl}phenolYield 45%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 4-[(4-bromophenyl)(cycloheptylidene)methyl]phenol (9) (0.20 g, 0.56 mmol) in DMF (5 mL) were added Pd(PPh3)2Cl2 (40 mg, 0.06 mmol), CuI (11 mg, 0.06 mmol), N,N-diisopropylethylamine (0.45 mL, 2.52 mmol) and 4-pentyn-1-ol (0.11 mL, 1.12 mmol). The reaction mixture was stirred at 80° C. overnight, poured into saturated aqueous NH4Cl (15 mL) and water (5 mL), extracted with ethyl acetate (3×50 mL). The combined organic phase was washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as brown oil. The crude product was purified by chromatography on a silica gel column eluted with a gradient from hexanes to 45% EtOAc in hexanes to give a light brown solid. The solid was triturated with hot hexanes containing 1% MeOH to afford 91 mg (45%) of the title compound (240) as beige solid. mp 125-126° C. 1H NMR (400 MHz, DMSO-d6): δ 1.49 (bs, 8H), 1.60-1.70 (m, 2H), 2.10-2.25 (m, 4H), 2.41 (t, J=7.0 Hz, 2H), 3.40-3.50 (m, 2H), 4.49 (t, J=5.2 Hz, 1H), 6.65 (d, J=8.4 Hz, 2H), 6.88 (d, J=8.4 Hz, 2H), 7.04 (d, J=8.0 Hz, 2H), 7.26 (d, J=8.2 Hz, 2H), 9.27 (s, 1H). LCMS (ESI): m/z 361 (M+H)+, 359 (M−H)−.

Workup

  1. extractionextracted with ethyl acetate (3×50 mL)
  2. washThe combined organic phase was washed with water, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customto give the crude product as brown oil
  7. customThe crude product was purified by chromatography on a silica gel column
  8. washeluted with a gradient from hexanes to 45% EtOAc in hexanes
  9. customto give a light brown solid
  10. customThe solid was triturated with hot hexanes containing 1% MeOH

Sources & evidence

ORD record
ord-247ff2397474489b9c69a8f7fe2e313b
Source dataset
uspto-grants-2010_09
Patent number
US07799828B2

Reaction notes

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